Note: Descriptions are shown in the official language in which they were submitted.
s
The present invention relates to certain new 2-
imidazolylmethyl-2-phenyl-1 ,3 dioxolanes, to a process
for thei.r production and to their use as fungicides.
It has already been disclosed that certain tri~
azolylalkanols possess fungicidal properties (see DE-OS
(German Published Specification) 2,431,407). Thus, for
example, 4 chlorophenyl-(1,2,4-triazol-1-yl-methyl)-
carbinol can be used for combating fungi. However, the
action o this substance is not always adequate,
particularly when low amounts are used.
Furthermore, it has already been disclosed that
certaln imidazolyl-alkanols exhibit good actions against
fungi which are pathogenic to humans ~see 7th Med. Chem.
12, 784 791 (1969)). Thus, for example, 4-bromophenyl-
(imidazol-l-yl-methyl)-carbinoL and 2,4-dichlorophenyl-
(imidazol-l-yl-methyl) carbinol can be employed for this
indication. However, the action of these compounds
against phytopathogenic fungi is not always satisfactory.
The present invention now provides, as new compound
the' 2-'imida201'ylmethyl-2-phenyl-1,3-dioxola'lles of' the
general formula
/==N
R ~ CH2 - N ~
R1 R~ (I)
in which
R represents a grouping the the general formula
CF3 or ~
~ represents a hydrogen atom or an alkyl group,
R2 represents a hydrogen atom or an alkyl or
halogenoalkyl group,
Le A 21 387
s
X represents a hydrogen or halogen atom or an alkyl, alkoxy,
nitro or cyano group,
n is 1 or 2, and
: Y is a phenoxy or phenyl group optionally substituted by at
least one radical selected from halogen and alkyl,
or a non-phytotoxic acid addition salt or meta.l salt complex
thereof wherein the metal is selected from those in main groups
II to IV and sub-groups I, II and IV to VIII of the periodic
table of elements.
The compounds of the formula (I) can occur in various
stereoisomeric forms; preferably, they occur in the form of
stereoisomer mixtures.
According to the present invention we further provide a
process for the production of a compound of the present invention
characterised in that a 1,3-dioxolane derivative of the general
formula R ~ CH2 - Z
1 ~ ~ 2 ~II)
in which
R, R1 and R2 have the meanings given above and
Z represents a halogen atom or a grouping of the general
formula -o-So2-R3,
wherein
R3 represents a methyl or p-methylphenyl group,
is reacted with an imidazole of the general formula
r N
M - N
(III)
--2--
7a~8s
in which
M represents a hydrogen atom or an alkali metal,
in the presence of a diluent and, if appropriate, in the presence
of an acid-binding agent, and, iE desired, an acid or metal salt
is then added onto the resulting compound of the formula (I).
2a-
87~5
--3--
-
Finally, it has bee.n found that the 2-i~idaz.ol.yl-
2-phenyl-1,3-dioxolanes according to the invention, of
the formula (I), and plant-tolerated acid addition salts
and metal salt complexes possess powerful fungicidal
properties,
Surprisingly, the substance~ according to the
invention exhibit a better fungicidal activity than the
compounds 4-chlorophenyl-(1,2,4-triazol-1-yl-methyl)-
carbinol, 4-bromophenyl-(imidazol l-yl-methyl)-carbinol
and 2,4-dichlorophenyl-(imidazol-1-yl-methyl)-carbinol,
which are known from the prior art and which are con-
stitutionally similar substances with the same direction
of actlon.
Preferred 2~imidazolyl~2-phenyl-1,3-dioxolanes of
formula (I) according to the present invention are those
in which
R represents a grouping of the general formula
CF3 Y
X ~ or ~
. R . re.pr.esents,a hydrogen,atom or,an,alkyl .group
having 1 to 4 carbon atoms;
R represents a hydrogen atom, an alkyl group
having 1 to 4 carbon atoms or a halogenoalkyl
group having 1 or 2 carbon atoms and 1 to 5
identical or different halogen atoms (such as
fluorine atoms and chlorine atoms);
X represents a hydrogen, fluorine, chlorine or
bromine atom or an alkyl or alkoxy group, each
having 1 to 4 carbon atoms;
.n.is l; and
Y represents an optionally substituted phenoxy or
substituted phenyl group, the following being
suitable substituents: halogen or alkyl having 1
to 4 carbon,atoms.
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8'7~85
Particularly preferred.-compounds of.the formula (I)
are those
in which
R represents a grouping of the general formula
1 CF3 or ~
R represents a hydrogen atom or an alkyl group
having 1 to 4 carbon atoms,
R represents a hydrogen atom or an unsubstituted
alkyl group having 1 to 4 car.bon atoms, and a
methyl group which is substituted by fluorine, or
chlorine;
X represents a hydrogen, fluorine or chlorine atom
or a methyl group;
n is l; and
Y represents an optionally substituted phenoxy or
~ substituted phenyl group (fluorine, chlorine and
; methyl being mentioned as substituents).
Preferred substances accordins to the invention are
: al.s.o .acid add.ition. s.al.ts of. 2.-imidazolylmeth.yl 2-phenyl-
1,3-dioxolanes of the formula (I), in which R, Rl and
R have the meanings mentioned as being preferred. Amongst
these substances, particularly preferred acid addition salts
are those which are formed b~ the addition of hydrohalic
acid (such as hydrobromic acid, and especially, hydrochloric
acid), phosphoric acid, nitric acid, sulphuric acid,
monofunctional and bi~unctional carboxylic acids and
hydrox~carboxylic acids (such as acetic acid, maleic acid,
~ succinic acid~ fumaric acid, tar.taric acid, citric acid,
: salic~clic acid, sorbic acid and lactic acid) and sulphonic
acids (such as p-toluenesulphonic acid and naphthalene-1,5-
disulphonic acid)
Metal salt complexes of 2-imidazolylmethyl-2-phenyl-
1,3-dioxolanes. of.the .formula (I),. in. which. R, Rl and. R2
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1~8~85
have the meanings mentioned as being preferred, are also
preferred substances according to the invention. Amongst
these substances, particularly preferred metal salt
complexes are those which contain, as cations, metals of
main groups II to IV or sub-groups I and II or IV to VIII
of the periodic table of elements, copper~ zinc, manganese,
magnesium, tin, iron and nickel ~eing mentioned as examples.
Anions of these metal salt complexes are preferably
those which are derived from hydrohalic acids, in
particular hydrochloric acid and hydrobromic acid, and
also phosphoric acid, nitric acid and sulphuric acid.
If, for example, 2-bromoethyl 2-(4-chloro-2-tri-
fluoromethyl-phenyl)-1,3-dioxolane and imidazole are used
as startingmaterials, the course of the reaction in the
process according to the invention can be represented by
the following equation:
CF3
Cl ~ ~ / ;H2ar H N ~ N Base
~ -H3r
5F3 /=N
C 1~>~< C H 2 ~
Preferred 1,3-dioxolane derivatives of formula (II)
re~uired as starting materials in carrying out the process
according to the invention are those in which R, Rl and R2
have the meanings which have already been mentioned for
; these radicals in the description of the preferred and
particularly preferred compounds according to the invention
and Z represents a chlorine or bromine atom or a grouping
; 25 of th~ general formula -o-So2-R3, wherein R3 represents
a methyl or p-methylphenyl group.
The 1,3-dioxolane derivatives of the formula (II) are
Le A 21 387
novel and form a :further subject of the presenk invention.
The present Invention thus provides, as new compounds,
the compounds of formula ~ , as deined above.
According to the present invention we further provide
5 a process ~or the production of compounds of formula (II~ -
characterised in that a keto derivative of the general
formula
R-C-CH2-Z (IV)
o
in which
lO R and 2 have the meanings given above,
is reacted with a diol of the general formula
HO OH (V)
R R2
in which
Rl and R2 have the meaning given above,
in the present of an inert organic solvent (such as
toluene) and. in the. pr.esence .of a s.trong a.cid as the
catalyst (such as p-toluenesulphonic acid) at a
temperature between 80 and lOO~C, if appropriate under
elevated pressure.
The keto derivatives of the formu.la (IV) are known
(see, for example, DE-OS (German Published Specification)
2,431,407), or are obtained in a generally known manner,
by reacting the corresponding ketones, for example, with
chlorine, or bromine in the presence of an inert organic
solvent (such as an ether or a chlorinated or unchlorinated
hydrocarbon) at room temperature, or reacting them with
customary chlorinating agents (such as sulphuryl chloride)
at 20 to 60~C. The sulphonic acid derivatives of the
compounds of the formula (IV) can likewise be prepared
according to known methods.
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'7~8~;i
-7
The diols of the ormula (V) are generally known
compounds of organic chemlstry; they are obtained in a
generally known manner.
Preferred imidazoles of formula (III) additionally
to be used as starting materials for the process according
to the invention are those in which M represents a hydrogen
atom, sodium or potassium.
The imidazoles of the formula (III) are generally
known compounds of organic chemistry.
Suitable diluents for the process according to
the invention are inert organic solvents. These pre-
ferably include amides, such as dimethylformamide or
dimethylacetamide; and also dimethylsulphoxide or hexa-
methylphosphoric acid triamide.
The process according to the invention is carried
out, if appropriate, in the presence of an acid binding
agent. It ls possible to add all the customarily usable
inorganic or organic acid-binding agents, such as
alkali metal carbonates (for example sodium carbonate,
potassium carbonate and sodium bicarbonate), or such as
lower tertiary alkylamines, cycloalkylamines or aralkyl-
amines (for example triethylamine, N,N~dimethylcyclo-
hexylamine, dicyclohexylamine and N~N-dimethylbenzylamine,
and Eurthermore pyridine and diazabicyclooctane). Pre-
ferably, an appropriate excess of imidazole is used.
In carrying out the process according to the invention,the reaction temperatures can be varied within a
relatively wide range. In general, the reaction is
carried out at a temperature between 20 and 150C,
preferably between 60 and 150C.
In carrying out the process according to the invention
1 to 2 mol o the imidazole of the formula (III) and,
if appropriate, 1 to 2 mol of an acid-binding agent
are preferably employed per mol of the compounds of the
formula (II). The compounds of the formula (I) are
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__,, . _ _ . , _ _ .. _ _ _ _ . . , . . .. . . . . . . __ _.. _ .
` i~l 3'7~35
isolated in a cus~omary manner. In some cases/ it is
advantageous to prepare the compounds of the formula (I)
in pure form via their salts.
Those acids which have already been mentioned in
connection with the description of the acid addition salts
according to the invention as being preferred acids are
preferred for the preparation of plant-tolerated acid
addition salts of the compounds of the formula (I).
These acid addition salts of the compounds of the
formula (I) can be obtained in a simple manner by customary
methods of salt formation for example by dissolving a
compound of the formula (I) in a suitable inert solvent
and adding the acid,for example hydrochloric acid, and
they can be isolated in a known manner, for example by
filtration, and if appropriate purified by washing with an
inert organic solvent. `
Salts of those anions and cations which have already
been mentioned in connection with the description of the
metal salt complexes according to the invention as being
preferred are preEerred for the preparation of metal salt
complexes of compounds of the formula ~I).
The metal salt complexes of compounds of the formula
(I) can be obtained in a simple manner by customary
processes, thus, for example, by dissolving the metal
salt in an alcohol, for example ethanol t and adding the
solution to the compound of the formula (I)o The metal
salt complexes can be isolated in a known manner, for
example by filtration, and if appropriate purified by
recrystallisation.
The active cornpounds according to the invention
exhibit a powerful microbicidal action and can be employed
in practice for combating undesired micro-organisms.
The active compounds are suitable for use as plant protec-
tion agents.
Fungicidal agents in plant protection are employed
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1 ~37~ 8S
g
for combating Plasmodiophoromycetes, Oomycetes, Chytridio-
mycetes, Zyyomycetes, Ascomycetes, Basidiomycetes and
Deuteromycetes.
The good toleration by plants, of the active ocmpounds,
at the concentrations required for combating plant
diseases, permits treatment of above-ground parts of plants,
of vegetative propagation stock and seeds, and of the soil.
As plant protection agents, the active compounds
accordlng to the invention can be used with particularly
good success for combating Podosphaera species r such as
against the powdery mildew of apple causative organism
(Podosphaera leucotricha), and for combating cereal dis-
eases, such as against the powdery mildew 3~ cereals
causative organism ~Erysiphe graminis) and against the
stripe disease of barley (Helminthosporium gramineum).
The compounds according to the invention also exhibit a
good m v o action, in particular against pathogens in
rice plants.
When used in appropriate concentrations, the substances
according to the invention also exhibit plant growth~
regulating properties.
The active compounds can be converted to the customary
formulations, such as solutions, emulsions, wettable
powders, suspensions, powders, d~sting agents, foams,
pastes, soluble powders, granules, aerosols, suspension-
emulsion concentrates, seed-treatment powders, natural and
synthetic materials impregnated with active compound, very
fine capsules in polymeric substances and in coating com
positions for seed, and formulations used with burning
equipment, such as fumigating cartridges, fumigating cans
and fumigating coils as well as ULV cold mist and warm
mist formulations.
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87~
--10--
These formulations may -be produced in known manner,
~or e~ampleby mixing the active compounds with extenders,
that is to say liquid or liquefied gaseous or solid diluents
or carriers, optionally with the use of surface-active
agents, that is to say emulsifying agents and/or dispersing
agents and/or foam-forming agents. In the case of the
use of wa~er as an extender, organic solvents can, for
example, also be used as auxiliary solvents.
As liquid diluents or carriers, especially solvents,
there are suitable in the main, aromatic hydrocarbons,
such as xylene, toluene or alkyl naphthalenes, chlorinated
aromatic or chlorinated aliphatic hydrocarbons, such as
chlorobenzenes, chloroethylenes or methylene chloride,
aliphatic or alicyclic hydrocarbons, such as cyclohexane
or paraffins, for example mineral oil fractions, alcohols,
such as butanol or glycol as well as their ethers and
esters, ketones, such as acetone, methyl ethyl ketoneg
methyl isobutyl ketone or cyclohexanone, or strongly
polar solvents, such as dimethylformamide and dimethyl-
sulphoxide, as well as water.
By liquefied gaseous diluents or carriers are meantliquids which ~ould be gaseous at normal temperature and
under normal pressure, for example aerosol propellants,
such as halogenated hydrocarbons as well as butane, propane,
nitrogen and carbon dioxide.
As solid carriers there may be used ground natural
minerals, such as kaolins, clays, talc, chalk, quartz,
attapulgite, montmorillonite or diatomaceous earth, and
ground synthetic minerals, such as highly-dispersed silicic
3 acid, alumina and silicates. As solid carriers for granules
there may be used crushed and fractionated natural rocks
such as calcite, marble, pumice, sepiolite and dolomite,
as well as synthetic granules of inorganic and organic
meals, and granules o~ organic material such as sawdust,
35 coconut shells, maize cobs and tobacco stalks.
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.. . _,, . _ . _ _ _ . _ . _ ... . _ . . .. . . . . .. . .. .. .. . . .. . . . . . . . . ... .
--11--
As emulsifying and/or foam-forming agents there may
be used non-ionic and anionic emulsifiers, such as polyoxy-
ethylene-fatty acid esters, polyoxyethylene-fatty alcohol
ethers, for example alkylaryl polyglycol ethers, alkyl
sulphonates, alkyl sulphates, aryl sulphonates as well
as albumin hydrolysis products. Dispersing agents include 3
for example, lignin sulphite waste li~uors and methyl-
cellulose.
Adhesives such as carboxymethylcellulose and
natural and synthetic polymers in the form of powders,
granules or latices, such as gum arabic, polyvinyl alcohol
and polyvinyl acetate, can be used in the formulations.
It is possible to use colorants such as inorganic
pigments, for example iron oxide~ titanium oxide and
Prussian Blue, and organic dyestuffs, such as alizarin
dyestuffs, azo dyestu~fs or metal phthalocyanine dyestuffs,
and trace nutrients~ such as salts of iron, manganese,
boron, copper, cobalt, molybdenum and zinc.
The formulations in general contain from 0.1
to 95 per cent by weight of active compound, preferably
from 0.5 to 90 per cent by weight.
The active compounds according to the invention can
be present in the formulations or in the various use forms
as a mixture with other known active compounds, such as
fungicides, bactericides, insecticides, acaricides,
nematicides~ herbicides, bird repellants, growth factors,
plant nutrients and agents for improving soil structure.
The active compounds can be used as such or in the
form of their formulations or the use forms prepared
therefrom by further dilution, such as ready-to-use
solutions, emulsions, suspensions, powders, pastes and
granules. They are used in the customary manner, for
example by watering 9 immersion, spraying, atomising,
misting~ vaporising, injecting, forming a slurry, brushing
on, dusting, scattering, dry dressing~ moist dressing~ wet
Le A 21 387
37~85
dressing, slurry dressing or encusting.
Especially in the treatment of parts of plants, the
active compound concentrations in the use forms can be
varied within a substantial range. They are, in general,
between l and 0.0001% by weight, preferably between 0.5
and O.C01%.
In the treatment of seed, amounts of active compound
of 0.001 to 5~ g per kilogram of seed, preferably
0.01 to lO g are generally required.
For the treatment of soil, active compound concentrations
of 0.00001 to 0.1% by weight, preferably 0.0001 to 0.02%
by weight are generally required at the place of action.
The present invention also provides fungicidal
composition containing as active ingredient a compound
of the present invention in admixture with a solid or
; liquefied gaseous diluent or carrier or in admixture
with a li~uid diluent or carrier containing a surface-
active agent.
The present invention also provides a method of
combating fungi which comprises applying to the fungi
or to a habitat thereof, a compound of the present invention
alone or in the form of a composition containing as active
ingredient a compound of the present invention in admixture
with a diluent or carrier.
The present invention further provides crops protected
from damage by Pungi by being grown in areas in which
immediately prior to and/or during the ~ime of the growing
a compound of the present invention was applied alone
or in admixture with a diluent or carrier.
It will be seen that the usual methods of providing
a harvested crop may be improved by the present invention.
The preparation and the use of the active compounds
according to the invention are illustrated by the
Examples which follow.
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~,
37~135
-13-
ti ~ rll~s
CF3 ~= N
Cl ~O ~ / CH2 - N ~
0 0 ~ HCl
3.9 g (0.0116 mol) of 2-bromomethyl-2-(4-chloro-2-
tri1uoeomethyl~phenyl)-1,3-dioxolane and 2.4 g (0.0348
mol) of imidazole in 50 ml of dimethylacetamide were heated
under reflux for 4 days~ After the reaction mixture had
cooled, it was dissolved in water and the solutlon was
extracted with etherO The ether phase was washed with
water, dried over sodium sulphate and concentrated.
Ethereal hydrochloric acid was added to the residual oil,
and the latter was brought to crystallisation by tritura-
tion. 2~(4-Chloro-2-trifluoromethyl-phenyl)-2-(imidazol-
l-methyl)-1,3-dioxolane hydrochloride of melting point
174 to 83C was obtained.
CF3
Cl ~<, CH2-Br
O O
35 g (0.12mol~ of 4-chloro-2-trifluoromethyl-
phenacyl bromide and 9 g (0.15 mol) of glycol were heated
in a water separator for 24 hours with 1.5 g of p-toluene-
sulphonic acid in 80 ml of toluene, in the presence of
20 ml of butanol. After the reaction mixture had
cooled, it was washed successively with dilute aqueous
sodlum hydroxide solution and with water, dried over
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; ., , ' .
.
. .
-14-
sodium sulphate and concentrated. 29.6 g (74~ of theory)
of crude 2-bromomethyl-2-(4-chloro-2-trifluoromethyl-
phenyl)-1,3-dioxolane were obtained as an oil, which was
directly reacted further.
CF3
Cl- ~ \ CH2-Br
~ -
1 ml o acetic acid was added to 22.3 g ( a .1 mol) of
4-chloro-2-trifluoromethyl-acetophenone in 200 ml of
chloroform~ and the mixture was warmed to 40C. 5.1 ml
(0.1 mol) of bromine in 50 ml of chloroform were added
dropwise at this temperature. The reaction mixture was
stlrred until the evolution of gas had ceased. After
the mixture had cooled, it was washed successively with
water and a~ueous sodium bicarbonate solution, dried over
sodium sulphate and concentrated. 29O4 g (97% of theory)
of crude 4-chloro-2-trifluoromethyl-phenacyl bromide were
obtained as an oil, which is directly reacted further.
The compounds of the formula
~=~N
R ~ CH2-N
R1 R2
which are listed in Table 1 below were also prepared
according to the method given in Example 1:
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: ~ - .
,
1~8~ 3S
--15--
Table 1
r
ample R Rl R2 Physical
No. constants
.
CF3
2 Cl ~ CH3 H viscous oil
CF3
3 Cl- ~ CH2Cl H viscous oil
CF3
4 Cl ~ C2H5 H viscous oil
Cl ~ H H M.~.: 220C
(~H~l)
~0
6 ~ H H viscous oil
~o ~xHCl)
7 ~ CH3 H viscous oil
(~ ~,~
CH2Cl H viscous oil
9 ~ ~ C2H5 H viscous oil
10 Cl ~ CH3 H viscous oil
11 Cl ~ ~ CH2Cl H viscous oil
12 Cl- ~ ~ C2H5 H viscous oil
13 Cl ~ ~ CH3 CH3 viscous oil
CF3
14 Cl ~ CH3 CH3 viscous oil
15 ~ O ~ CH3 ~H3 viscous oil
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- _ .
:~:
'
-
87~1~5
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The fungicidal activity of the compounds of this
invention is illustrated by the following biotest Examples.
In these Examples, the compounds according ~o the
present invention are each identified by the number (given
in brackets) of the corresponding preparative Example,
which will be found later in this speci~ication.
; The known comparison compounds are identified as
follows:
(A) = Cl ~ CH - CH2 - N
OH ~=N
(B) =Br ~ ~H-CH2-N ~
C1 OH ~--N
Example A
Erysiphe test (barley)/protective/
Solvent: 100 parts by weight of dimethylformamide
Emulsifie;r: 0.25 part by weight. of..a.Lk.ylar.yl polyglycol
ether
To produce a suitable preparation of active
compound, 1 part by weight of act.ive compound was mixed with
the stated amounts of solvent and emulsifier, and the
concentrate was diluted with water to the desired concen-
tration.
To test for protective activity, young plants
were sprayed with the preparation of active compound until
dew-moist. After the spray coating had dried on, the
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. .
1~8~6~85
- 17 -
plants were dusted with spores of Erysiphe graminis f.sp.
hordei.
The plants were placed in a greenhouse at a
temperature of about 20C and a relative atmospheric
S humidity of about 80%, in order to promote the development
of powdery mildew pustules.
Evaluation was carried out 7 days after the
inoculation.
In this test, a clearly superior activity compared
with the prior art was shown, for example, by the
compounds (2) and (4).
Example_B
Drechslera graminea test (barley) / seed treatment
(syn. Helminthosporium gramineum)
The active compounds were used as dry dressingsO
These were prepared by extending the particular active
compound with a ground mineral to give a finely pulverulent
mixture, which ensured uniform distribution on the seed
surface~
To apply the dressing, the infected seed was
shaken with the dressing in a closed glass flask for 3
minutes.
The seed was embedded in sieved, moist standard
soil and was exposed to a temperature of 4C in closed
Petri dishes in a refrigerator for 10 days. Germination
of the barl~y, and possibly also of the fungus spores, was
thereby initiated. 2 batches of 50 yrains of the
pregerminated barley were subsequently sown 3 cm deep in
standard soil and were cultivated in a greenhouse at a
temperature of about 18C, in seedboxes which were exposed
to light for 15 hours daily.
About 3 weeks after sowing, the plants were
evaluated for symptoms of stripe disease.
In this test, a clearly superior activity
compared with the prior art was shown, for example, by the
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_ .. _ , , ,., .. _ _ .. . . . . .. . . . . ..... , . . . . . . . . . . ... . _
. .
'7~5
- 18 -
compounds (1) and (~).
Podosphaera test (apple) / protective
Solvent: 4.7 parts by weight of acetone
Emulsifier: 0.3 part by weight of alkylaryl polyglycol
ether
~ To produce a suitable preparation of active
: compound, 1 part by weight of active compound was mixed with
; the stated amounts of solvent and emulsifier, and the
concentrate was diluted with water to the desired concen-
tration.
To test for protective activity, young plants were
sprayed with the preparation of ac~ive compound until
dripplng wet. After the spray coating had dried on,
the plants were inoculated by dusting with conidia of the
powdery mildew of apple causative organism (Podosphaera
leucotricha).
The plants were then placed in a greenhouse at
23C and a relative atmospheric humidity of about 70%.
Evaluation was carried out 9 days after the
inoculation~
In this test, a clearly superior activity compared
with the prior art was shown, for example, by the
compounds (2)., (4) and (1).
Le A 21 387
.
~ ,
.
